in vivo

Hiroshi Ohno
Cell fusion may create niche for
immune cell education
Researchers identify possible precursors of lymphoid tissue cellular
network
Figure
Lymphoid follicle-like structures contain
FDC (red) with B220 + characteristics
(green).
©Blood/The American Society of
Hematology/110/1215 (2007)
Japanese researchers have identified a subset of cells they believe may induce the formation of a network
of follicular dendritic cells (FDC) in the spleen and lymph nodes.
A recent paper published by Hiroshi Ohno and colleagues at the RIKEN Research Center for Allergy and
Immunology, Yokohama, suggests that in the mouse, spleen cells expressing the cell surface marker proteins
CD35, involved in processing and clearance of immune complexes, and B220, found on almost all immune
system cells, can induce the formation of these networks and ultimately lymphoid follicles (Figure).
These so-called FDC form a reticular network of cells in the spleen and lymph nodes that trap immune
complexes of antibodies, antigens and associated molecules. The network plays a critical role in the development
and maturation of the antibody-producing B lymphocytes (B cells). If a B cell binds weakly to an
antigen trapped on the surface of an FDC, it undergoes programmed cell death (apoptosis). On the other
hand, a B cell that has a high affinity for the trapped antigen survives to become an antibody-producing
plasmablast, and ultimately a memory B cell. This is the fundamental process that underpins the ability of the
immune system to respond quickly to attack by pathogenic infection.
But it is not simply a matter of recognition; it appears that a complex interaction of cells and molecules
and cellular architecture within the dynamic microenvironment of the lymphoid follicle is required for B cell
maturation. The players include connective tissue cells called stromal cells.
“The intrigue of the lymphoid follicle stems from the complexity of its microarchitecture, comprising immune
cells and stromal cells, adhesion molecules, cytokines
and antigen-antibody complexes, and the relationships between
these components, in the formation of B cell-follicular
dendritic cell aggregates and the regulation of B cell differentiation,”
says Takaya Murakami, the first author of the paper.
Results from a series of experiments both in vitro and in
vivo suggest that the splenic cells with the CD35 and B220
proteins on their surface (CD35 + B220 + cells) interact with
stromal cells to create a niche for migrating B cells, forming
cell clusters. The researchers believe that this may play a
critical role in FDC network development and the subsequent
formation of lymphoid follicles. There is also some evidence
that the stromal cells may fuse with the CD35 + B220 + cells
during this process.
Further investigation of the role of stromal cells in the
development of the lymphoid follicles and B cell maturation is
planned, says Murakami.
Takuya Murakami
ORIGINAL RESEARCH PAPER
Murakami, T., Chen, X., Hase, K., Sakamoto, A., Nishigaki, C. & Ohno, H. Splenic CD19 - CD35 + B220 + cells function as an
inducer of follicular dendritic cell network formation. Blood 110, 1215–1224 (2007).
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This article is reproduced from RIKEN RESEARCH with permission
http://www.rikenresearch.riken.jp/research/330/